Morphologic and biochemical information relating to critical events during gliogenesis is limited. The present proposal is designed to study neuroglial and neuronal factors that are likely to affect glial proliferation and differentiation. The present study will combine morphologic, autoradiographic and biochemical techniques to study these factors. Normal development and an experimental model of disease will be investigated. The experimental model is the mouse mutant Jimpy which fails to form myelin in the Central Nervous System. The studies will use autoradiographic techniques to study and compare cell proliferation between the normal and experimental models. The biochemical studies will examine differences in the incorporation and uptake of components used in the manufacture of myelin. A combination of quantitative histologic and autoradiographic (3H-thymidine and 2(14C)-deoxyglucose) studies will be employed to correlate the development of the neuroglial and myelin heterogeneity along the optic system with the vascularization of the nerve and with possible differences in regional metabolism. The effects of hypo- and hyperthyroidism upon myelination and gliogenesis will be quantitatively evaluate using light and electron microscopy. Our observations that the female mouse carrying the Jimpy gene exhibits mosaicism provides the basis for continued histologic and biochemical studies of the interaction between genetically different cells in this mutant.